Abstract: Objectives Drug-coated balloon (DCB) angioplasty is a potential treatment for intracranial atherosclerotic stenosis (ICAS) patients. Since the vascular anatomy differed in anterior and posterior circulation,the perioperative complications tend to vary. This study aimed to compare the therapeutic effect and safety of DCB angioplasty in ICAS treatment in both anterior and posterior circulations. Methods This analysis included symptomatic severe ICAS patients who underwent DCB angioplasty at Xuanwu Hospital,Capital Medical University. Participants were divided into two groups based on the location of the culprit lesion,the anterior circulation (Ac) group and posterior circulation (Pc) group. Baseline demographics,plaque features,and clinical outcomes were compared between the two groups. Results A total of 94 eligible patients were included in this analysis (53 cases in Ac group and 41 cases in Pc group). There was no significant difference between the two groups in terms of perioperative risks of any stroke or death (Ac:5.7% 3/53 vs. Pc:4.9% 2/41;OR 2.91,95% confidential interval CI 0.33~25.99). After adjustment,the Ac group had a significantly higher risks of iatrogenic arterial dissection (Ac:45.3% 24/53 vs. Pc:12.2% 5/41;aOR 4.72,95% CI 1.49~14.90) and remedial stenting (Ac:26.4% 14/53 vs. Pc:2.4% 1/41;aOR 14.71,95% CI 1.61~134.37) than the Pc group. Conclusion The safety of DCB angioplasty for treating ICAS in both anterior and posterior circulations is comparable. However,DCB in anterior circulation may lead to more arterial dissections and rescue stenting. Long-term follow-up and further studies were necessary to further confirm ICAS treatment strategies.